During the millions of years that animals and plants have competed among themselves for food and space, parasites have invaded practically every kind of living organism. The fact that many parasites cause diseases is of particular concern to the health of humans and animals throughout the world.
Discovery of drugs effective against helminth parasites has been an endeavor of rare successes. Finding molecules that safely cure infections by a diverse array of parasitic helminths presents a strong challenge, one that has so far been met only through the laborious process of screening synthetic compounds or fermentation extracts for toxicity to whole organisms. A useful broad spectrum anthelmintic class has been discovered about once per decade, but it has now been almost 20 years since the prototype of the newest class, the avermectins, was found. The dearth of useful new anthelmintic templates can be blamed on many factors, but an undeniable cause is the inefficiency of current methods for discovering parasiticides, which have not kept pace with improvements made in other therapeutic arenas. See Geary, T. G. et al., International Journal for Parasitology, Vol. 25, No. 11, pp.1273-1280 (1995).
FMRFamide-related peptides (FaRPs) are ubiquitous neuropeptides of invertebrates and have profound physiological effects on their neuromuscular systems. These neuropeptides are not found in vertebrates, making them attractive targets for anthelmintic discovery. A number of FMRFamide-related peptides have now been isolated from representative nematodes and other helminths, arthropods, molluscs and annelids, which offers the possibility of specific targeting of these parasites and other invertebrate parasites and insects. See Price, D. A. and Greenberg, M. J., Biological Bulletin, Vol. 177, pp. 190-205 (1989); Stretton, A. O. W. et al., Parasitology, Vol. 102, pp. S107-S116 (1991); Maule, A. G. et al., Parasitology, Vol. 109, pp. 351-356 (1994); Geary, T. G. et al., International Journal for Parasitology, Vol. 25, No. 11, pp.1273-1280 (1995); Halton, D. W., et al., Advances in Parasitology, Vol. 34, pp. 163-227 (1994); Walker, R. J., Comparative Biochemistry and Physiology, Vol. 102C, pp. 213-222 (1992); Maule, A. G. et al., Parasitology, Vol. 113, Supplement pp S119-S135 (1996); Maule, A. G. et al., Parasitology Today, Vol. 12, No. 9, pp 351-357 (1996).
The present invention provides a new method of screening molecules in order to identify compounds useful as anthelmintic drugs. The present invention provides a novel radioactive FMRFamide-related peptide as a screening tool in receptor binding assays for detecting candidate anthelmintic molecules, in which molecules are not assessed for the ability to cause effects on the whole organism, but the ability to interact with a specific molecular target. The novel radioactive FMRFamide-related peptide of the present invention has potent bioactivity in Ascaris suum neuromuscular strips. Therefore, used as a screening tool in a mechanism-based receptor binding assay, it can provide information on thousands of test compounds in a short period of time while utilizing limited amounts of radioligand, drug, and animal tissue.